The purpose of this study is an intensive evaluation to define the mechanisms responsible for insulin resistance in the obese adolescent. To attempt to circumvent some of the problems derived from interpretation of tolerance tests, we plan to utilize constant infusion techniques to set up steady state conditions of glucose and insulin so as to study other modifying variables (growth hormone, glucagon, cortisol, triglycerides, free fatty acids and the amino acid alanine). Pertubations of this system will then be introduced to gain further kinetic information and quantitate the relative importance of each of these variables on insulin levels both in the basal state and after stimulation. Gastrointestinal factors as well as parasympathetic and adrenergic modulation of insulin secretion will be monitored by measurement of gut glucagon-like material by immunoassay and the use of atropine and alpha and beta blocking agents. Qualitative alteractions of peripheral fuel utilization will be documented using respiration quotient determinations during each of the experimental conditions and in addition body composition data including cell size and cell number will be ascertained in each individual. These studies will contribute to our understanding of the hormonal, metabolic and tissue factors important in glucohomeostatic mechanisms and may provide new insight into the pathogenetic mechanisms underlying the obese state in childhood. Documentation of hormonal, metabolic or tissue factors important in the development of childhood obesity would lead to more rational and successful approaches to the prevention and treatment of obesity. BIBLIOGRAPHIC REFERENCES: Darki, Abdul, Fiser, Robert H., and Beard, Alice: Gluconeogenesis in the Large for Gestational Age Infant Following Alanine Loading, Clinical Research, Vol. 24, January, 1976, p. 60A. Fiser, Jr.,R. H., Sperling, Mark A., and Bray, George A.: Glucagon Secretary in Childhood Obestiy. Clinical Research, Vol 24, January, 1976, p. 73A.